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Wednesday, March 22, 2017

Doctors Say: Deadly Spider Venom Could Ward Off Stroke Brain Damage

Ingredient in funnel web spider venom can
protect cells from being destroyed by a stroke, even when given hours after the
event, study shows

Doctors have stumbled on an unlikely source for a drug to ward
off brain damage caused by strokes: the venom of one of the deadliest spiders
in the world.

A bite from an Australian funnel web spider can kill a human in 15 minutes, but a harmless
ingredient found in the venom of one species can protect brain cells from being
destroyed by a stroke, even when given hours after the event, scientists say.

If the compound fares well in human trials, it could become the
first drug that doctors have to protect against the devastating loss of neurons
that strokes can cause.

Researchers discovered the protective molecule by chance as they
sequenced the DNA of toxins in the venom of the Darling Downs funnel web spider
(Hadronyche infensa) that lives in Queensland and New South Wales.

Venom from three spiders was gathered for the study after scientists
trapped and “milked exhaustively” three spiders on Orchid beach, about 400km
north of Brisbane.

The molecule, called Hi1a, stood out because it looked like two
copies of another brain cell-protecting chemical stitched together. It was so
intriguing that scientists decided to synthesise the compound and test its
powers. “It proved to be even more potent,” said Glenn King at the University
of Queensland’s centre for pain research.

Strokes occur when blood flow to the brain is interrupted and
the brain is starved of oxygen. About 85% of strokes are caused by blockages in
blood vessels in the brain, with the rest due to bleeds when vessels rupture.
Approximately six million people a year die from stroke, making it the second
largest cause of death worldwide after heart attacks.

When a stroke happens, the oxygen level in the brain drops. This
forces the brain to burn its primary fuel, glucose, very differently. Instead
of oxidising glucose for energy, the brain switches to a process called
anaerobic glycolysis. The reaction releases energy to keep the brain working,
but it also produces acid, which can cause brain cells to die.

In a series of studies on rats, King showed that a single small
dose of the spider venom molecule protected neurons from induced strokes. The
compound works by blocking what are called ion channels in cells, specifically
those that respond to the onset of acidic conditions in the brain.

Reporting in the journal, Proceedings of the National Academy of Sciences,
King describes how administering Hi1a two hours after stroke reduced the extent
of brain damage in rats by 80%. But the compound was still effective eight
hours after stroke, reducing the amount of brain damage by about 65% when
compared with untreated animals.

Rats that had the compound recovered far better than those that
went without. “The untreated rats performed very badly after stroke. Their
neurological and motor performance were terrible,” said King. But treatment
with Hi1a “almost restored these functions to normal,” he added.

The researchers hope to start human trials of the compound in
the next two years, but have more experiments to perform first. These will test
whether the molecule works in all cases of stroke and is safe to use when blood
vessels rupture in the brain, rather than become blocked. In the latest study,
the compound was infused directly into the brain, but the scientists have found
since that nasal deliver works too.

If trials show that the compound works, it could potentially
transform the treatment of stroke patients. There are no drugs on the market
that can protect the brain from stroke injuries. The best hospitals can offer
are infusions of clot-busting drugs if a clot is to blame, or a surgical
procedure called endovascular thrombectomy, which physically pulls the clot
from the brain

Before doctors can administer clot-busting drugs,
they must confirm with a brain scan that the stroke was caused by a blockage.
This is because the treatment thins the blood and could make matters worse if
the stroke was caused by a haemorrhage.

If Hi1a is found to be safe for people
who have had with brain bleeds, it could be given to patients as soon as they
reach a doctor.

“The drug could be given in the ambulance to most stroke
patients before hospital arrival, maximising the number of neurons that can be
saved,” said King. “This should diminish the mortality from stroke and provide
much better outcomes for those that survive as more brain function will be
retained.”

Kate Holmes at theStrokeAssociation,
said it was unknown whether Hi1a could be an effective treatment in humans. “We
welcome any treatment that has the potential to reduce the damage caused by
stroke, particularly if this can benefit people who are unable to arrive at
hospital quickly,” she added. “Current treatments must be given in half this
time period and it is too early for us to know if this research can offer an
alternative for stroke patients.

“We urge for stroke to be treated as an emergency.
The sooner a person can get to hospital after a stroke, the sooner the right
treatment can be received which can improve survival and help recovery,” she
said.

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